tbuckley/cabot-search huggingface dataset:
Splenomegaly in patients with primary or secondary myelofibrosis who are candidates for allogeneic hematopoietic cell transplantation: a Position Paper on behalf of the Chronic Malignancies Working Party of the EBMT
Authors: Nicola Polverelli, Juan Carlos Hernández-Boluda, Tomasz Czerw, Tiziano Barbui, Mariella D'Adda, Hans Joachim Deeg, Markus Ditschkowski, Claire Harrison, Nicolaus Martin Kröger, Ruben Mesa, Francesco Passamonti, Francesca Palandri, Naveen Pemmaraju, Uday Popat, Damiano Rondelli, Alessandro Maria Vannucchi, Srdan Verstovsek, Marie Robin, Antonio Colecchia, Luigi Grazioli, Enrico Damiani, Domenico Russo, Jessica Brady, David Patch, Slawomir Blamek, Gandhi Laurent Damaj, Patrick Hayden, Donal P McLornan, Ibrahim Yakoub-Agha
Journal: The Lancet Haematology (2022)
Brain cancer after radiation exposure from CT examinations of children and young adults: results from the EPI-CT cohort study
Authors: Michael Hauptmann, Graham Byrnes, Elisabeth Cardis, Marie-Odile Bernier, Maria Blettner, Jérémie Dabin, Hilde Engels, Tore S Istad, Christoffer Johansen, Magnus Kaijser, Kristina Kjaerheim, Neige Journy, Johanna M Meulepas, Monika Moissonnier, Cecile Ronckers, Isabelle Thierry-Chef, Lucian Le Cornet, Andreas Jahnen, Roman Pokora, Magda Bosch de Basea, Jordi Figuerola, Carlo Maccia, Arvid Nordenskjold, Richard W Harbron, Choonsik Lee, Steven L Simon, Amy Berrington de Gonzalez, Joachim Schüz, Ausrele Kesminiene
Journal: The Lancet Oncology (2022)
Leveraging an established neighbourhood-level, open access wastewater monitoring network to address public health priorities: a population-based study
Authors: Devin A Bowes, Erin M Driver, Simona Kraberger, Rafaela S Fontenele, LaRinda A Holland, Jillian Wright, Bridger Johnston, Sonja Savic, Melanie Engstrom Newell, Sangeet Adhikari, Rahul Kumar, Hanah Goetz, Allison Binsfeld, Kaxandra Nessi, Payton Watkins, Akhil Mahant, Jacob Zevitz, Stephanie Deitrick, Philip Brown, Richard Dalton, Chris Garcia, Rosa Inchausti, Wydale Holmes, Xiao-Jun Tian, Arvind Varsani, Efrem S Lim, Matthew Scotch, Rolf U Halden
Journal: The Lancet Microbe (2022)
Drug-loaded balloon with built-in NIR controlled tip-separable microneedles for long-effective arteriosclerosis treatment
Authors: Li Huang, Huaqiang Fang, Teng Zhang, Binbin Hu, Shichen Liu, Fanzhen Lv, Zhaoxia Zeng, Huijie Liu, Weimin Zhou, Xiaolei Wang
Journal: Bioactive Materials (2022)

Drug-eluting balloon (DEB) angioplasty has emerged as an effective treatment for cardiovascular and cerebrovascular diseases. However, distal embolism and late lumen restenosis could be caused by drug loss during DEB handling and rapid drug metabolization. Here, a drug-loaded balloon equipped with tip-separable microneedles on the balloon surface (MNDLB) was developed. Inbuilt near-infrared (NIR) ring laser inside the catheter inner shaft was introduced to activate the biodegradable microneedle tips for the first time. The drug-loaded tips thus could be embedded in the vasculature and then released antiproliferative drug - paclitaxel slowly via polymer degradation for more than half a year. A significant increase in drug delivery efficiency and superior therapeutic effectiveness compared with the standard DEB were demonstrated using an atherosclerosis rabbit model.
Prophylaxis of posterior capsule opacification through autophagy activation with indomethacin-eluting intraocular lens
Authors: Xiaobo Zhang, Jing Wang, Jingwei Xu, Wen Xu, Yin Zhang, Chenqi Luo, Shuang Ni, Haijie Han, Xingchao Shentu, Juan Ye, Jian Ji, Ke Yao
Journal: Bioactive Materials (2022)

Posterior capsule opacification (PCO) is the most common long-term postoperative complication of cataract surgery, leading to secondary vision loss. Optimized intraocular lens (IOL) structure and appropriate pharmacological intervention, which provides physical barriers and biological inhibition, respectively, can block the migration, proliferation, and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) for PCO prophylaxis. Herein, a novel indomethacin-eluting IOL (INDOM-IOL) with an optimized sharper edge and a sustained drug release behavior was developed for PCO prevention. Indomethacin (INDOM), an ophthalmic non-steroidal anti-inflammatory drug (NSAID) used for postoperative ocular inflammation, was demonstrated to not only be able to suppress cell migration and down-regulate the expression of cyclooxygenase-2 (COX-2) and EMT markers, including alpha-smooth muscle actin (α-SMA) and cyclin D1, but also promote the autophagy activation in LECs. Additionally, autophagy was also verified to be a potential therapeutic target for the down-regulation of EMT in LECs. The novel IOL, serving as a drug delivery platform, could carry an adjustable dose of hydrophobic indomethacin with sustained drug release ability for more than 28 days. In the rabbit PCO model, the indomethacin-eluting IOL showed excellent anti-inflammatory and anti-PCO effects. In summary, indomethacin is an effective pharmacological intervention in PCO prophylaxis, and the novel IOL we developed prevented PCO
Erratum to ‘Identification of a distinct NK-like hepatic T-cell population activated by NKG2C in a TCR-independent manner’ [J Hepatol 77 (2022) 1059-1070]
Authors: June-Young Koh, Min-Seok Rha, Seong Jin Choi, Ha Seok Lee, Ji Won Han, Heejin Nam, Dong-Uk Kim, Jae Geun Lee, Myoung Soo Kim, Jun Yong Park, Su-Hyung Park, Dong Jin Joo, Eui-Cheol Shin
Journal: Journal of Hepatology (2022)
Mannose metabolism normalizes gut homeostasis by blocking the TNF-α-mediated proinflammatory circuit
Authors: Peng Xiao, Ziwei Hu, Jiaheng Lang, Tianyuan Pan, Randall Tyler Mertens, Huilun Zhang, Ke Guo, Manlu Shen, Hongqiang Cheng, Xue Zhang, Qian Cao, Yuehai Ke
Journal: Cellular and Molecular Immunology (2022)
Targeting CD89 on tumor-associated macrophages overcomes resistance to immune checkpoint blockade
Authors: Lijun Xu, Bingyu Li, Chenyu Pi, Zhaohua Zhu, Fei Tao, Kun Xie, Yan Feng, Xiaoqing Xu, Yanxin Yin, Hua Gu, Jianmin Fang
Journal: Journal for ImmunoTherapy of Cancer (2022)

Despite the survival benefits observed with immune checkpoint blockade (ICB) treatment-programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1), many patients with cancer have not benefited from these agents because of impaired antigen presentation and other resistance mechanisms. To overcome resistance to checkpoint therapy, we designed bispecific antibodies (BsAbs) targeting CD89 and tumor antigens. We demonstrated their immunomodulatory efficacy as a separate treatment strategy or combined with immune checkpoint inhibitors. We have previously generated a heterodimeric one-arm IgG1 Fc-based bispecific antibody. For animal efficacy studies, murine tumors in a humanized transgenic mice model were used to determine the effects of CD89-bispecific antibodies on antigen presentation and immune cell recruitment. The efficacy of the CD89 bispecific antibody against tumors resistant to pembrolizumab was evaluated in double-transgenic mice. BsAbs targeting CD89 on tumor-associated macrophages (TAMs) increased the ratio of M1:M2 and activated the antigen presentation, leading to increased cytotoxic T cell-mediated tumor regression. CD89-BsAbs also potentiated a combinational antitumor effect with PD-1/PD-L1 inhibitors and overcame the ICB resistance by augmenting cytotoxic T-cell infiltration and reshaping tumor immune microenvironment. In an hCD89/hPD-1 double transgenic mouse model engrafted with pembrolizumab-resistant B16-HER2 tumor cells, the HER2-CD89 bispecific antibody potently inhibited tumor growth. CD89 BsAbs targeting tumor antigens and TAMs controlled tumor growth in animal models by improving antigen presentation and T-cell infiltration. Our results suggest a general strategy for overcoming resistance to ICB.
A Tale of 3 Tracers
Authors: Ismaheel O. Lawal, Omotayo Atinuke Adediran, Saima Muzahir, Sarah Friend, Manali Ajay Bhave, Jane Meisel, Mylin A. Torres, Toncred Marya Styblo, Cathy Graham, Anna Holbrook, Kevin Kalinsky, Bridget Fielder, Ronald J. Crowe, Gary A. Ulaner, David M. Schuster
Journal: Clinical Nuclear Medicine (2022)

Abstract A 41-year-old woman with invasive lobular carcinoma of the breast underwent sequential 68 Ga-PSMA-11 PET/CT and 18 F-fluciclovine PET/CT as part of an ongoing clinical trial (NCT04750473). 68 Ga-PSMA PET/CT showed increased radiotracer uptake in the uterine endometrium and left adnexa. 18 F-fluciclovine PET/CT showed increased radiotracer uptake in a leiomyomatous uterus. A clinical 18 F-FDG PET/CT demonstrated radiotracer uptake in the endometrium and a circumferential area of uptake in the left adnexa, a pattern more similar to the 68 Ga-PSMA uptake pattern. This case highlights the discordance in the uptake pattern of 2 radiotracers approved for prostate cancer imaging but increasingly used in non-prostate malignancies imaging.
Association of Recreational Cannabis Legalization With Cannabis Possession Arrest Rates in the US
Authors: Christian Gunadi, Yuyan Shi
Journal: JAMA Network Open (2022)

Importance Recreational cannabis legalization (RCL) has been advocated as a way to reduce the number of individuals interacting with the US criminal justice system; in theory, however, cannabis decriminalization can achieve this objective without generating the negative public health consequences associated with RCL. It is still unclear whether RCL can bring additional benefits in terms of reducing cannabis possession arrests in states that have already decriminalized cannabis. Objective To examine whether RCL was associated with changes in cannabis possession arrests in US states that had already decriminalized cannabis during the study period and whether these changes differed across age and racial subgroups. Design, Setting, and Participants This repeated cross-sectional study used cannabis possession arrest data from the Federal Bureau of Investigation Uniform Crime Reporting Program (UCRP) for US states from 2010 through 2019. Statistical analysis was conducted from October 6, 2021, to October 12, 2022. Exposures Implementation of statewide RCL. Main Outcomes and Measures Cannabis possession arrest rates per 1000 population per year were assessed with a quasi-experimental difference-in-differences design and were used to estimate the association of RCL with arrest rates in RCL states that had or had not decriminalized cannabis before RCL. This association was also examined in subgroups for age (adults vs youths) and race (Black vs White). Results This study included UCRP data for 31 US states, including 9 states that implemented RCL during the study period (4 without and 5 with decriminalization) and 22 non-RCL states. In the 4 states that had not decriminalized cannabis before legalization, RCL was associated with a 76.3% decrease (95% CI, −81.2% to −69.9%) in arrest rates among adults. In the 5 states that had already decriminalized cannabis, RCL was still associated with a substantial decrease in adult arrest rates (−40.0%; 95% CI, −55.1% to −19.8%). There was no association of RCL with changes in arrest rates among youths. In addition, changes in arrest rates associated with RCL did not differ among Black and White individuals. Conclusions and Relevance In this repeated cross-sectional study, RCL was associated with a sizable reduction in cannabis possession arrests among adults in states that had already decriminalized cannabis during the study period (2010-2019), albeit the magnitude was smaller compared with states that had not decriminalized cannabis before RCL. In addition, RCL did not seem to be associated with changes in arrest rates among youths or disparities in arrest rates among Black and White individuals.
Author Correction: Disrupted Ca2+ homeostasis and immunodeficiency in patients with functional IP3 receptor subtype 3 defects
Authors: Julika Neumann, Erika Van Nieuwenhove, Lara E. Terry, Frederik Staels, Taylor R. Knebel, Kirsten Welkenhuyzen, Kourosh Ahmadzadeh, Mariah R. Baker, Margaux Gerbaux, Mathijs Willemsen, John S. Barber, Irina I. Serysheva, Liesbeth De Waele, François Vermeulen, Susan Schlenner, Isabelle Meyts, David I. Yule, Geert Bultynck, Rik Schrijvers, Stephanie Humblet-Baron, Adrian Liston
Journal: Cellular and Molecular Immunology (2022)
Activation of Phosphodiesterase 3A: New Hope for Cardioprotection
Authors: Mario Chiong, Miles D. Houslay, Sergio Lavandero
Journal: Circulation (2022)

ypertension is a major cause of cardiovascular disease and premature death worldwide.The World Health Organization has estimated that, in 2019, 626 million women and 652 million men 30 to 79 years of age had hypertension, most living in low-and middle-income countries.In 2015, 8.5 million deaths were associated with high blood pressure. 1The early detection and the severity of end-organ damage and secondary diseases are critical determinants of cardiovascular prognosis in patients with hypertension.Cardiac hypertrophy is a frequent end-organ sequela associated with hypertension, increasing the risk of heart failure, sudden death, myocardial infarction, and stroke. 2
In THA or TKA, risk for symptomatic VTE was higher with aspirin vs. enoxaparin at 90 d
Authors: David Garcia
Journal: Annals of Internal Medicine (2022)

Source Citation CRISTAL Study Group; Sidhu VS, Kelly TL, Pratt N, et al. Effect of aspirin vs enoxaparin on symptomatic venous thromboembolism in patients undergoing hip or knee arthroplasty: the CRISTAL randomized trial. JAMA. 2022;328:719-27. 35997730
Comparison of Uptake and Prices of Biosimilars in the US, Germany, and Switzerland
Authors: David L. Carl, Yannic Laube, Miquel Serra-Burriel, Huseyin Naci, Wolf-Dieter Ludwig, Kerstin N. Vokinger
Journal: JAMA Network Open (2022)

Importance Biologics account for a substantial proportion of health care expenditures. Their costs have been projected to reach US $452 billion in global spending by 2022. Given recent expiration of patent protection of biologics, a shift toward greater follow-on competition among biosimilars would be expected that would allow greater uptake and lower drug costs. Objective To assess uptake and prices of biosimilars in the US compared with 2 European countries (Germany and Switzerland) with national mechanisms for drug price negotiation. Design, Setting, and Participants In this cohort study, biologics and biosimilars that were approved in the US, Germany, and Switzerland until August 2020 were identified. Prices and sales data were extracted from public and commercial databases for the years 2011 to 2020. Data were analyzed from August 1, 2021, to February 28, 2022. Main Outcomes and Measures Descriptive statistics were used to show temporal trends in the uptake of biosimilars and relative prices compared with those of reference products (ie, biologic agents) for each country. Descriptive analysis was also performed to compare the uptake of biosimilars between the 3 countries limited to biologics that have biosimilars on the market in all countries. To test if biosimilar awareness in each country increased over the last decade, a linear least squares regression was applied. Results The study cohort included 15 biosimilars and 6 biologics for the US, 52 biosimilars and 15 biologics for Germany, and 28 biosimilars and 13 biologics for Switzerland. Uptake of biosimilars increased over time in all countries. On average, the biosimilar market share at launch was highest in Germany; however, it increased at the fastest rate in the US. Monthly treatment costs of biosimilars in the US were a median of 1.94 (IQR, 1.78-2.44) and 2.74 (IQR, 1.91-3.46) higher than corresponding costs in Germany and Switzerland, respectively. Conclusions and Relevance The findings of this cohort study suggest that more biosimilars have been marketed in Germany and Switzerland than in the US. Policies that counter anticompetitive practices in the US could allow biosimilars to enter the market sooner and could also lower health care costs with improved access. Awareness of biosimilars should be promoted to increase uptake of biosimilars globally.
BP-lowering drugs reduced major CV events by similar amounts in patients with and without type 2 diabetes
Authors: Jayson C. Carr
Journal: Annals of Internal Medicine (2022)

Source Citation Nazarzadeh M, Bidel Z, Canoy D, et al. Blood pressure–lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis. Lancet Diabetes Endocrinol. 2022;10:645-54. 35878651
Reverse Triggering during Controlled Ventilation: From Physiology to Clinical Management
Authors: Antenor Rodrigues, Irene Telias, L. Felipe Damiani, Laurent Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Reverse triggering dyssynchrony is a frequent phenomenon recently recognized in sedated critically ill patients under controlled ventilation. It occurs in at least 30-55% of these patients and often occurs in the transition from fully passive to assisted mechanical ventilation. During reverse triggering, patient inspiratory efforts start after the passive insufflation by mechanical breaths. The most often referred mechanism is the entrainment of the patient's intrinsic respiratory rhythm from the brainstem respiratory centers to periodic mechanical insufflations from the ventilator. However, reverse triggering might also occur because of local reflexes without involving the respiratory rhythm generator in the brainstem. Reverse triggering is observed during the acute phase of the disease, when patients may be susceptible to potential deleterious consequences of injurious or asynchronous efforts. Diagnosing reverse triggering might be challenging and can easily be missed. Inspection of ventilator waveforms or more sophisticated methods, such as the electrical activity of the diaphragm or esophageal pressure, can be used for diagnosis. The occurrence of reverse triggering might have clinical consequences. On the basis of physiological data, reverse triggering might be beneficial or injurious for the diaphragm and the lung, depending on the magnitude of the inspiratory effort. Reverse triggering can cause breath-stacking and loss of protective lung ventilation when triggering a second cycle. Little is known about how to manage patients with reverse triggering; however, available evidence can guide management on the basis of physiological principles.
In CV disease, clopidogrel reduces nonfatal MI and MACE vs. aspirin but not stroke or mortality
Authors: Akshay Goel, Aaqib H. Malik
Journal: Annals of Internal Medicine (2022)

Source Citation Tasoudis PT, Kyriakoulis IG, Sagris D, et al. Clopidogrel monotherapy versus aspirin monotherapy in patients with established cardiovascular disease: systematic review and meta-analysis. Thromb Haemost. 2022;122:1879-87. 35577054
Computed Tomographic Radiomics in Differentiating Histologic Subtypes of Epithelial Ovarian Carcinoma
Authors: Mandi Wang, Jose A. U. Perucho, Yangling Hu, Moon Hyung Choi, Lujun Han, Esther M. F. Wong, Grace Ho, Xiaoling Zhang, Philip Ip, Elaine Y. P. Lee
Journal: JAMA Network Open (2022)

Importance Epithelial ovarian carcinoma is heterogeneous and classified according to the World Health Organization Tumour Classification, which is based on histologic features and molecular alterations. Preoperative prediction of the histologic subtypes could aid in clinical management and disease prognostication. Objective To assess the value of radiomics based on contrast-enhanced computed tomography (CT) in differentiating histologic subtypes of epithelial ovarian carcinoma in multicenter data sets. Design, Setting, and Participants In this diagnostic study, 665 patients with histologically confirmed epithelial ovarian carcinoma were retrospectively recruited from 4 centers (Hong Kong, Guangdong Province of China, and Seoul, South Korea) between January 1, 2012, and February 28, 2022. The patients were randomly divided into a training cohort (n = 532) and a testing cohort (n = 133) with a ratio of 8:2. This process was repeated 100 times. Tumor segmentation was manually delineated on each section of contrast-enhanced CT images to encompass the entire tumor. The Mann-Whitney U test and voted least absolute shrinkage and selection operator were performed for feature reduction and selection. Selected features were used to build the logistic regression model for differentiating high-grade serous carcinoma and non–high-grade serous carcinoma. Exposures Contrast-enhanced CT-based radiomics. Main Outcomes and Measures Intraobserver and interobserver reproducibility of tumor segmentation were measured by Dice similarity coefficients. The diagnostic efficiency of the model was assessed by receiver operating characteristic curve and area under the curve. Results In this study, 665 female patients (mean [SD] age, 53.6 [10.9] years) with epithelial ovarian carcinoma were enrolled and analyzed. The Dice similarity coefficients of intraobserver and interobserver were all greater than 0.80. Twenty radiomic features were selected for modeling. The areas under the curve of the logistic regression model in differentiating high-grade serous carcinoma and non–high-grade serous carcinoma were 0.837 (95% CI, 0.835-0.838) for the training cohort and 0.836 (95% CI, 0.833-0.840) for the testing cohort. Conclusions and Relevance In this diagnostic study, radiomic features extracted from contrast-enhanced CT were useful in the classification of histologic subtypes in epithelial ovarian carcinoma. Intraobserver and interobserver reproducibility of tumor segmentation was excellent. The proposed logistic regression model offered excellent discriminative ability among histologic subtypes.
99mTc-Pyrophosphate Scintigraphy Can Image Tracer Uptake in Skeletal Trunk Muscles of Transthyretin Cardiac Amyloidosis
Authors: Koji Takahashi, Yoshiyasu Hiratsuka, Daisuke Sasaki, Tomoki Sakaue, Daijiro Enomoto, Hiroe Morioka, Shigeki Uemura, Takafumi Okura, Shuntaro Ikeda, Taizo Kono, Takaaki Iwamura, Nobuhisa Yamamura, Sohei Kitazawa, Mitsuharu Ueda
Journal: Clinical Nuclear Medicine (2022)

99mTc-pyrophosphate (99mTc-PYP) uptake in the skeletal muscles is minimal in patients with transthyretin cardiac amyloidosis (ATTR-CA) when assessed qualitatively and quantitatively. We previously demonstrated moderate- to high-grade 99mTc-PYP uptake in the subcutaneous abdominal fat of some patients with ATTR-CA and showed that this abnormal finding could reflect the regional amyloid burden of this tissue. We aimed to investigate the frequency of 99mTc-PYP uptake in skeletal trunk muscles of patients with ATTR-CA.Chest- and abdomen-centered 99mTc-PYP scintigraphy images were obtained 2 hours after IV injections of the tracer (20 mCi) in 36 patients with ATTR-CA. The frequency of 99mTc-PYP uptake in the following 11 skeletal trunk muscles was investigated: pectoralis major, deltoid, subscapularis, infraspinatus, trapezius, latissimus dorsi, erector spinae, psoas major, abdominal oblique, rectus abdominis, and the gluteus muscles.Ten of the 11 muscles were involved in patients with the highest number of 99mTc-PYP uptake in the skeletal trunk muscles examined, whereas no muscle was involved in a patient with the least uptake. The muscle with the highest rate of 99mTc-PYP uptake, observed in 34 of 36 patients (94.4%), was the abdominal oblique. No tracer uptake was observed in the psoas major. The frequency of radiotracer uptake in the remaining examined muscles was between those of abdominal oblique and psoas major muscles.Radiotracer uptake was often detectable in some skeletal trunk muscles of ATTR-CA, although the muscles of patients examined and the skeletal trunk muscles of 1 patient showed heterogeneity in the uptake of 99mTc-PYP.